title: Clinical significance and prognostic value of microRNA expression signatures in hepatocellular carcinoma.
abstract: OBJECTIVE
  MicroRNAs (miRNAs) play important roles in the development and progression of cancer. The aim of this study is to identify miRNA expression signatures in hepatocellular carcinoma and delineate their clinical significance for hepatocellular carcinoma.
  
  
  METHODS
  Patients with hepatocellular carcinoma, undergoing hepatectomy were randomly divided into training set (60 patients) and test set (50 patients). Other 56 patients were used as an independent cohort. The miRNA expression levels were detected by microarray and verified by quantitative real-time reverse transcription-PCR (qRT-PCR).
  
  
  RESULTS
  A 30-miRNA signature consisting of 10 downregulated and 20 upregulated miRNAs was established for distinguishing hepatocellular carcinoma from noncancerous liver tissues in the training set with 99.2% accuracy. The classification accuracies of this signature were 97% and 90% in the test set and independent cohort, respectively. The expression level of four miRNAs in the 30-miRNA signature was verified by qRT-PCR in the training set. Twenty miRNAs were then selected to construct prognostic signature in the training set. Of the 20 miRNAs, six were risk factors and 14 were protective factors. A formula based on the 20 miRNAs was built to compute prognostic index. Kaplan-Meier analysis showed that patients with a higher prognostic index had a significantly lower survival than those with a low index. This was verified in the test and independent sets. Multivariate analysis indicated that the 20-miRNA signature was an independent prognostic predictor.
  
  
  CONCLUSIONS
  The 30- and 20-miRNA signatures identified in this study should provide new molecular approaches for diagnosis and prognosis of patients with hepatocellular carcinoma and clues for elucidating molecular mechanism of hepatocarcinogenesis.
authors.affiliation: State Key Laboratory of Oncology in South China, Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Wei
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Huang
authors.forename: Mei-Yin
authors.initials: MY
authors.lastname: Zhang
authors.forename: Bin-Kui
authors.initials: BK
authors.lastname: Li
authors.forename: Hui-Zhong
authors.initials: HZ
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.forename: Xiao-Qian
authors.initials: XQ
authors.lastname: Chen
authors.forename: Long
authors.initials: L
authors.lastname: Huang
authors.forename: Qing-Ming
authors.initials: QM
authors.lastname: Zhou
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Jia
authors.forename: X F Steven
authors.initials: XF
authors.lastname: Zheng
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Yuan
authors.forename: Hui-Yun
authors.initials: HY
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D059467:Transcriptome
chemical_list: D035683:MicroRNAs